The overall objective of this proposal is to develop an integrated system to optimize PDT dose for interstitial photodynamic therapy (PDT). We explore an explicit method to characterize the PDT dose. The explicit PDT dose is essentially the product of drug concentration and light fluence for a given photosensitizer and tissue oxygenation. To quickly determine the spatial distribution of tissue optical properties in-vivo at the treatment wavelength, we plan to develop a motorized device consists of multiple detectors and point sources. To determine the spatial distribution of drug concentration in-vivo, we plan to develop a fluorescence spectroimaging system. In addition, we plan to develop an absorption spectroimaging system to determine the distribution of absorption spectra of tissue. Proper analysis of the absorption spectrum determines tissue oxygenation, and also provides another estimate of the photosensitizer concentration in the prostate gland. To determine the temporal-spatial distribution of light fluence rate, we use our existing in-vivo light dosimetry system in combination the multi-detector probes. The measured results can be compared with calculations using information about tissue optical properties and a suitable light fluence algorithm in heterogeneous medium. We hypothesize that PDT dose, once above a threshold dose, correlates to the tumor necrosis. We also hypothesize that there are heterogeneities of both optical properties and drug concentration within the treatment volume (e.g., prostate gland). This requires in-situ PDT dosimetry (of light fluence rate and drug distribution), feedback, and light source adjustment as part of the integrated system. With an accurate calculation of the PDT dose and the use of optimization methods, we can adjust the light source weights to achieve the most efficacious distribution of PDT dose, treating the tumor to dose prescription yet avoiding injury to normal structure.